associations of sleep disturbance with adhd: implications ...frequently coincident with sleep...
TRANSCRIPT
REVIEW ARTICLE
Associations of sleep disturbance with ADHD: implicationsfor treatment
Allan Hvolby
Received: 9 April 2014 / Accepted: 8 July 2014 / Published online: 17 August 2014
� The Author(s) 2014. This article is published with open access at Springerlink.com
Abstract Attention-deficit/hyperactivity disorder
(ADHD) is commonly associated with disordered or dis-
turbed sleep. The relationships of ADHD with sleep
problems, psychiatric comorbidities and medications are
complex and multidirectional. Evidence from published
studies comparing sleep in individuals with ADHD with
typically developing controls is most concordant for asso-
ciations of ADHD with: hypopnea/apnea and peripheral
limb movements in sleep or nocturnal motricity in poly-
somnographic studies; increased sleep onset latency and
shorter sleep time in actigraphic studies; and bedtime
resistance, difficulty with morning awakenings, sleep onset
difficulties, sleep-disordered breathing, night awakenings
and daytime sleepiness in subjective studies. ADHD is also
frequently coincident with sleep disorders (obstructive
sleep apnea, peripheral limb movement disorder, restless
legs syndrome and circadian-rhythm sleep disorders).
Psychostimulant medications are associated with disrupted
or disturbed sleep, but also ‘paradoxically’ calm some
patients with ADHD for sleep by alleviating their symp-
toms. Long-acting formulations may have insufficient
duration of action, leading to symptom rebound at bedtime.
Current guidelines recommend assessment of sleep dis-
turbance during evaluation of ADHD, and before initiation
of pharmacotherapy, with healthy sleep practices the first-
line option for addressing sleep problems. This review aims
to provide a comprehensive overview of the relationships
between ADHD and sleep, and presents a conceptual
model of the modes of interaction: ADHD may cause sleep
problems as an intrinsic feature of the disorder; sleep
problems may cause or mimic ADHD; ADHD and sleep
problems may interact, with reciprocal causation and pos-
sible involvement of comorbidity; and ADHD and sleep
problems may share a common underlying neurological
etiology.
Keywords Sleep � ADHD � Stimulant � Amfetamine �Methylphenidate � Atomoxetine
Introduction
Attention-deficit/hyperactivity disorder (ADHD) is a
common neurodevelopmental disorder that has been esti-
mated to affect approximately 5.3 % of children and ado-
lescents worldwide (Polanczyk et al. 2007) and to persist
into adulthood in approximately two-thirds of patients
(Spencer et al. 1998; Wender 1998). Inattention, hyperac-
tivity and impulsiveness are recognized as the symptoms of
ADHD according to the current diagnostic criteria [Diag-
nostic and Statistical Manual of Mental Disorders (DSM),
Fifth Edition (American Psychiatric Association 2013;
Casas et al. 2013) and International Classification of Dis-
eases and Related Health Problems, 10th Revision (ICD-
10) (World Health Organization 1992)] and are associated
with characteristic behavioral difficulties and impairments
of day-to-day functioning. Although diagnosis relies on
observations made while patients are awake, the prevalence
of sleep disturbances in individuals with ADHD is reported
to be in the range 25–55 % (Corkum et al. 1998; Hodgkins
et al. 2013; Owens 2005; Sung et al. 2008). In a recent
Australian study, 62 % of children with ADHD had mod-
erate or severe sleep problems and 22 % took sleep med-
ications during the 1-week observation period (Efron et al.
2014). Indeed, high nocturnal activity and disordered sleep
A. Hvolby (&)
Department of Child and Adolescent Psychiatry, Psychiatry of
Southern Denmark, Gl. Vardevej 101, 6715 Esbjerg N, Denmark
e-mail: [email protected]
123
ADHD Atten Def Hyp Disord (2015) 7:1–18
DOI 10.1007/s12402-014-0151-0
were defining characteristics of ‘hyperkinetic reaction in
childhood’ or ‘attention deficit disorder’ in earlier versions
of the DSM (American Psychiatric Association 1980;
Barkley 1990; Sadeh et al. 2006; Spruyt and Gozal 2011).
The association of sleep with ADHD is multifaceted and
complex. Problems with sleep may be an intrinsic feature
of ADHD, or may both exacerbate and be exacerbated by
the symptoms of the disorder. Problems with sleep can,
however, also lead to the development of ADHD or
ADHD-like symptoms, potentially resulting in misdiagno-
sis (Cortese et al. 2006b; Owens 2008). The effects of
restricted, disordered or disturbed sleep can manifest as
symptoms, behaviors or functional impairments that are
remarkably similar to those of ADHD (Beebe 2006; Gruber
2009; O’Brien 2009). The interrelationships are further
complicated by the use of psychostimulant medications to
treat ADHD, which impair sleep in some patients (Spruyt
and Gozal 2011) but paradoxically (Bradley 1937) improve
sleep in others via a calming effect (Jerome 2001; Kins-
bourne 1973; Kooij et al. 2001; Kratochvil et al. 2005). For
these reasons, it has been recommended that primary sleep
disorders should be ruled out before initiating ADHD
medication (Cortese et al. 2013a; Lecendreux and Cortese
2007). Behavioral interventions targeted at improving sleep
may benefit some patients (Cortese et al. 2013a) and should
form part of the multimodal ADHD management plan
recommended for patients receiving pharmacotherapy
(Graham et al. 2011; Lecendreux and Cortese 2007; Wol-
raich et al. 2011).
Psychiatric comorbidities are common in children with
ADHD: up to 87 % of children with an ADHD diagnosis
have at least one comorbidity, and 20 % have three or more
comorbid conditions (Hodgkins et al. 2013; Rowland et al.
2002; Spruyt and Gozal 2011). Psychiatric illnesses such as
bipolar disorder, autism, post-traumatic stress disorder and
obsessive compulsive disorder often occur coincidently
with ADHD, and are also associated with sleep problems,
which may both result from and exacerbate comorbid
psychiatric symptoms (Ivanenko et al. 2004). Problems
with sleep are likely to have adverse effects on health-
related quality of life for children with ADHD and their
families (Hvolby et al. 2008; Saxby and Morgan 1993) and
may also contribute to the development of comorbid anx-
iety, depression or oppositional defiant disorder (Breslau
et al. 1996; Hvolby et al. 2008; Mick et al. 2000). The
interactions of comorbid disorders and associated medica-
tions with ADHD and sleep disturbances are therefore
important to consider when managing patients.
The complex, multidirectional interactions of sleep with
ADHD, medication and psychiatric comorbidities remain
unclear despite extensive research. The reciprocal nature of
the relationships between ADHD and sleep may reflect the
functional and neuroanatomical overlap between brain
regions involved in attention, arousal and sleep regulation
(Owens et al. 2013; Owens 2008). This review provides a
broad but comprehensive overview of the relationships
between ADHD and sleep, with the aims of fostering
greater understanding of the sleep-related issues faced by
many individuals with ADHD and of informing the phar-
macological and non-pharmacological management of the
disorder. In support of these aims, this article presents a
conceptual model of the potential interactions of sleep with
ADHD which is intended as an aid in the interpretation of
evidence related to the interactions of sleep problems with
ADHD and with medications used to treat ADHD.
Measuring sleep in patients with ADHD
Objective measures (polysomnography, actigraphy and the
multiple sleep latency test [MSLT]) and subjective mea-
sures (e.g., parent- or self-rated questionnaires and diaries)
are used to assess sleep in patients with ADHD.
Polysomnography
Polysomnography involves simultaneous and continuous
measurement of multiple physiological parameters, and is
usually conducted in a sleep laboratory. A combination of
electroencephalography, electrocardiography, electromy-
ography, electrooculography, pneumography and pulse
oximetry is typical, sometimes together with audiovisual
recordings.
Polysomnography is considered the ‘gold standard’ for
the objective measurement of sleep (Cortese et al. 2009;
Owens 2008), but is subject to a number of limitations.
Children’s sleep patterns may be affected by the unfamiliar
environment of the sleep laboratory or by the recording
apparatus (Beebe 2011; Bessey et al. 2013). At least some
polysomnographic parameters are subject to ‘first-night
effects,’ whereby sleep characteristics on a single night
may differ from those recorded on subsequent nights (Katz
et al. 2002; Kirov et al. 2012; Lorenzo and Barbanoj 2002;
Sadeh et al. 2006; Scholle et al. 2003).
Three published meta-analyses of polysomnographic
studies have investigated sleep in children with ADHD and
typically developing controls (Cortese et al. 2006a, 2009;
Sadeh et al. 2006). In a meta-analysis of 11 studies, the only
statistically significant polysomnographic finding was a
higher incidence of periodic limb movements in sleep
(PLMS) in children with ADHD than in controls (Sadeh et al.
2006). A subsequent meta-analysis of studies in non-medi-
cated patients included 5 of these 11 studies and 4 additional
polysomnographic studies (Cortese et al. 2009), and updated
a previous analysis by the same group (Cortese et al. 2006a).
Statistically significant polysomnographic findings were
2 A. Hvolby
123
lower sleep efficiency, higher apnea–hypopnea index (AHI)
and a larger number of sleep stage shifts per hour in children
with ADHD than in controls (Cortese et al. 2009). Data on
limb movements could not be pooled in this meta-analysis,
but the authors noted that the included studies were consis-
tent in describing elevations in indices of PLMS or general
sleep movements in children with ADHD compared with
controls (Cortese et al. 2006a, 2009). Since publication of
these meta-analyses, four individual polysomnographic
studies in un-medicated children with ADHD versus controls
have each reported no statistically significant differences in
any polysomnographic index, including PLMS, AHI and
sleep efficiency (Choi et al. 2010; Gruber et al. 2012a; Pri-
hodova et al. 2010, 2012), and one study has reported sta-
tistically significant differences in almost all of the
polysomnographic parameters assessed (Silvestri et al.
2009). This study also indicated that children with hyper-
active symptoms had a higher mean PLMS index than those
with predominantly inattentive ADHD (Silvestri et al. 2009).
Polysomnographic data in adults with ADHD are scarce
(Yoon et al. 2012), with one study reporting no significant
differences (Philipsen et al. 2005) and one reporting signif-
icant differences in four indices, compared with controls
(Sobanski et al. 2008).
Several studies have reported changes in rapid eye
movement (REM) sleep in children and adolescents with
ADHD (Golan et al. 2004; Gruber et al. 2009; Kirov et al.
2004; O’Brien et al. 2003a, b). Inter-study inconsistencies in
whether REM sleep is increased or decreased in patients with
ADHD compared with controls have been ascribed to chan-
ges in REM sleep during maturation (Kirov and Brand 2014).
However, three meta-analyses of polysomnographic studies
found no significant alterations in REM sleep parameters in
children with ADHD compared with controls (Cortese et al.
2006a, 2009; Sadeh et al. 2006). The most recent and inclu-
sive of these ruled out inter-study heterogeneity as being
responsible for the lack of any detectable pooled difference in
REM sleep parameters (Cortese et al. 2009).
In summary, the available evidence from polysomno-
graphic studies is most concordant for associations of
ADHD with apnea/hypopnea and PLMS/nocturnal motor
activity in children (Cortese et al. 2006a; Spruyt and Gozal
2011). The number of studies is limited, and some
parameters have been reported in only one or two studies,
indicating a need for additional research (Cortese et al.
2009). For example, two studies of sleep microstructure
(the cyclic alternating pattern) in patients with ADHD have
yielded inconsistent results (Miano et al. 2006; Prihodova
et al. 2012). Furthermore, current polysomnographic indi-
ces may not be sensitive enough to detect subtle patterns of
sleep fragmentation (Owens et al. 2013; Yoon et al. 2012).
For example, episodes of PLMS in children with ADHD
are reportedly characterized by atypical, low periodicity
movements which may not register on all polysomno-
graphic indices of PLMS, yet these may be more likely
than highly periodic, stereotypical PLMS to be associated
with arousal and sleep disturbance (Ferri et al. 2013).
Polysomnographic studies are generally small (typically
20–30 participants per arm), and there is a need for larger-
scale, multicenter studies (Cortese et al. 2009; Sadeh et al.
2006). Sleep parameters in children with ADHD are
influenced by age, gender, comorbidities, ADHD diag-
nostic criteria and subtype, and the inclusion of an adap-
tation night (to compensate for first-night effects), but these
variables are not controlled in many studies (Sadeh et al.
2006). In particular, the different diagnostic criteria used in
different studies may be an important factor underlying the
inconsistency of polysomnographic findings across studies
(Gomes et al. 2013; Kirov and Brand 2014; Kirov et al.
2004). Furthermore, children with ADHD often show
marked intra-individual variability and instability in sleep
parameters, rather than a consistent level of impairment
(Gruber and Sadeh 2004; Gruber et al. 2000; Hvolby et al.
2008; Lecendreux and Cortese 2007; Lecendreux et al.
2000; Moreau et al. 2013; Prihodova et al. 2010).
Actigraphy
Actigraphy involves wearing a sensor, usually on the wrist,
to measure motor activity. Current devices are small,
lightweight, unobtrusive and convenient. Despite the
increasing use of actigraphy in pediatric studies, variations
remain in the device used, the point of attachment, the
parameters measured and the method for storing and ana-
lyzing the signals (Meltzer et al. 2012). Actigraphy is
unable to provide information on sleep architecture, PLMS,
snoring or apnea/hypopnea. Compared with polysomnog-
raphy, actigraphy may overestimate waking after sleep
onset and underestimate total sleep time, and may also
underestimate sleep onset latency (presumably because
immobility generally precedes sleep) (Spruyt et al. 2011).
Nevertheless, actigraphy has the unique advantage of
providing a non-invasive means of measuring sleep–wake
patterns objectively over extended periods of time under
everyday conditions.
A meta-analysis of four actigraphic studies reported
statistically significantly longer mean sleep onset latency
and shorter true sleep time in non-medicated children with
ADHD than in typically developing controls (Cortese et al.
2009). Figure 1 illustrates data from one of these studies
and shows that mean actigraphic sleep onset latency was
longer in children with ADHD than in community controls
and children with other psychiatric conditions (Hvolby
et al. 2008). Mean longest sleep latency was also highest in
children with ADHD, but total sleep time did not signifi-
cantly differ among the three groups (Hvolby et al. 2008).
Associations of sleep disturbance with ADHD 3
123
In subsequent actigraphic studies, differences between
children with and without ADHD in sleep latency, sleep
efficiency and total sleep time were statistically significant
in one study (Moreau et al. 2013) but not in another (Wiebe
et al. 2013). Waking after sleep onset was found to be
increased in adolescents with ADHD (Mullin et al. 2011),
and several actigraphic measures of sleep have also been
reported to differ significantly in adults with ADHD,
compared with controls (Boonstra et al. 2007; Gamble
et al. 2013; Kooij et al. 2001; Van Veen et al. 2010). Ac-
tigraphic studies have also reported instability or increased
night-to-night variability in sleep parameters in patients
with ADHD compared with controls (Gruber and Sadeh
2004; Gruber et al. 2000; Hvolby et al. 2008; Moreau et al.
2013).
Multiple sleep latency test
The MSLT provides a measure of daytime sleepiness by
timing the first signs of sleep during daytime nap periods
(Spruyt and Gozal 2011). The technique is subject to
substantial heterogeneity, possibly due to differences in
methodology and patient populations among studies (Cor-
tese et al. 2009; Golan et al. 2004; Lecendreux et al. 2000).
In meta-analyses (Cortese et al. 2006a, 2009), the average
time taken to fall asleep in MSLTs was statistically sig-
nificantly shorter in patients with ADHD than in controls,
based on two included studies (Golan et al. 2004; Le-
cendreux et al. 2000). Both studies also reported that
greater proportions of children with ADHD fell asleep
during testing than did controls (Golan et al. 2004; Le-
cendreux et al. 2000). More recent studies have found no
significant differences between children with ADHD and
controls in MSLT outcomes (Prihodova et al. 2010; Wiebe
et al. 2013), although one of these reported statistically
significant inter-test variability in the ADHD group (Pri-
hodova et al. 2010). There is also little agreement among
three studies that have investigated the question of whether
MSLT results correlate with objective measures of noc-
turnal sleep in individuals with ADHD (Golan et al. 2004;
Lecendreux et al. 2000; Wiebe et al. 2013).
Subjective assessments
Subjective measures of sleep in children are based on
parent or child reports and include the BEARS sleep
screening tool (Owens and Dalzell 2005), the Children’s
Sleep Habits Questionnaire (CSHQ) (Owens et al. 2000),
the Children’s Sleep Behavior Scale (CSBS) (Fisher et al.
1989) and sleep diaries (Hvolby et al. 2008, 2009). Adult
instruments include the Pittsburgh Sleep Quality Index
(Buysse et al. 1989). Instruments for subjective assessment
of daytime sleepiness include the Epworth Sleepiness
Scale.
The most recent meta-analysis of subjective studies
found that ADHD was associated with statistically signif-
icant greater impairments in six parent-reported subjective
measures of sleep in children than in controls (Cortese
et al. 2009). The largest standardized mean difference was
observed for bedtime resistance, followed by difficulty
with morning awakenings, sleep onset difficulties, sleep-
disordered breathing, night awakenings and daytime
sleepiness. Other sleep problems reportedly associated with
ADHD in children and/or adults include early and middle
insomnia, nocturnal awakening, nocturnal activity, snoring,
breathing difficulties, restless sleep, parasomnias, night-
mares, daytime sleepiness, delayed sleep phase, short sleep
time and anxiety around bedtime (Hansen et al. 2013;
Hvolby et al. 2008, 2009; Spruyt and Gozal 2011; Yoon
et al. 2012).
Association of particular sleep problems with ADHD
subtypes
Different patterns of sleep impairment may be character-
istic of ADHD subtypes (Gruber 2009). Some studies show
that parent-reported sleep disturbances are more common
in combined-type ADHD than in predominantly inattentive
ADHD (Corkum et al. 1999; Mayes et al. 2009), while
others describe greater daytime sleepiness in predomi-
nantly inattentive ADHD than in combined-type ADHD
0
10
20
30
40
50
60
70
Psychiatricreferral and
ADHD diagnosis(n = 45)
Psychiatricreferral
(non-ADHD)(n = 64)
Randomlyselected fromlocal school
(n = 97)
Sle
ep o
nset
late
ncy
(min
utes
)Actigraphic measure
Parental estimate
Fig. 1 Sleep onset latency assessed by parental estimation and
actigraphy (Hvolby et al. 2008). Data are shown as means ± standard
deviations. Differences between the three groups were statistically
significant for both the actigraphic measure (p \ 0.01) and the
parental measure (p \ 0.001), as was the difference between the two
measures (p \ 0.001) across all groups (three-way analysis of
variance, adjusted for sex and family type) (Hvolby et al. 2008).
ADHD attention-deficit/hyperactivity disorder
4 A. Hvolby
123
(Chiang et al. 2010; LeBourgeois et al. 2004; Lecendreux
et al. 2000). However, differences in symptom severity
between subtypes may confound the associations with
sleep problems (Corkum et al. 2011). Hyperkinetic disorder
(HKD) diagnosed according to the ICD-10 criteria is
generally regarded as a more severe form of combined-type
ADHD than that described by the DSM, and children with
HKD exhibited profound sleep-related problems in a study
using subjective parent ratings (Gomes et al. 2013). If
different sleep problems are associated with different
ADHD subtypes, then this represents another potentially
uncontrolled variable in studies investigating the relation-
ship between sleep and ADHD (Kirov et al. 2004).
Agreement and disagreement between subjective
and objective measures of sleep
While laboratory studies are susceptible to artifacts (e.g.,
first-night effects), naturalistic studies are subject to
uncontrolled variables such as parents’ work schedules,
parenting style, family structure, child habits and
employment in teenagers (Beebe 2011). Several studies
have revealed discrepancies between results obtained
using objective and subjective measures of sleep in
patients with ADHD (Choi et al. 2010; Corkum et al.
2001; Hvolby et al. 2008; Lim et al. 2008; Owens et al.
2009; Wiggs et al. 2005; Yoon et al. 2012). In one study
in children, parental estimates of sleep onset latency
exceeded actigraphic estimates in about 75 % of cases,
although mean sleep onset latency was longer in children
with ADHD than in controls using both measures (Fig. 1)
(Hvolby et al. 2008). Subjective reports may emphasize
particularly problematic nights, which may not be cap-
tured in a single night’s objective measurement, or by
averaging objective measurements over several nights:
indeed, intra-individual variability in sleep parameters is
reportedly higher in patients with ADHD than in controls
(Gruber and Sadeh 2004; Gruber et al. 2000; Lecendreux
and Cortese 2007; Moreau et al. 2013; Tsai and Huang
2010). Parental sensitivity to behavioral problems at
bedtime may also lead to differences compared with
objective assessments (Hvolby et al. 2008; Owens et al.
2009; Yoon et al. 2012). In adults with ADHD, self-
reported sleep time, quality and efficiency were lower
than in controls, but this was found to correlate with
polysomnographic measures of PLMS and not with
polysomnographic measures of sleep efficiency, length or
onset latency (Philipsen et al. 2005). In summary, the
available methods for assessing sleep each present their
own advantages and disadvantages, with no single tech-
nique providing a complete picture of the complex
interactions between sleep and ADHD.
Relationship of sleep disorders to ADHD
Diagnosis of sleep disorders is based on formal subjective
and/or objective criteria, such as the International Classi-
fication of Sleep Disorders (American Academy of Sleep
Medicine 2005). Specific sleep disorders are associated
with ADHD or ADHD-like symptoms, and systematic
screening for sleep problems and disorders has been rec-
ommended during initial assessment and ongoing man-
agement of patients with ADHD (Cortese et al. 2013a).
Inadequate sleep in children is known to have neurocog-
nitive, neurobehavioral and functional manifestations that
overlap with the core features of ADHD (O’Brien 2009;
Owens et al. 2013). Experimental sleep restriction impacts
on attention and higher-level cognitive function (Beebe
2011), and has been shown to affect neurobehavioral
functioning in typically developing children (Gruber et al.
2011). No experimental study has yet shown that sleep
restriction induces hyperactivity, impulsivity or external-
izing behaviors in children (Beebe 2011), despite the per-
ception that ‘paradoxical’ hyperactivity exists as a
behavioral response to daytime sleepiness (Owens et al.
2013; Owens 2008). Recent observational studies in typi-
cally developing children have, however, shown that short
sleep duration correlates with ADHD-like symptoms and
behaviors scored by parents (Paavonen et al. 2009; Pesonen
et al. 2010) and teachers (Gruber et al. 2012b).
Sleep-disordered breathing and obstructive sleep apnea
The term sleep-disordered breathing (SDB) describes a
spectrum of conditions ranging from obstructive sleep
apnea (OSA) to primary snoring (O’Brien 2009; Owens
2008). SDB has been consistently associated with neuro-
behavioral and neurocognitive deficits, including inatten-
tive or ADHD-like symptoms (Beebe 2006; Beebe et al.
2004; Chervin et al. 2002, 2012; Gottlieb et al. 2003; Lal
et al. 2012; O’Brien 2009; Owens 2008; Rosen et al. 2004;
Soylu et al. 2013; Suratt et al. 2011). Furthermore, a recent
systematic review indicated that the prevalence of OSA in
patients with ADHD (25–30 %) is higher than in the
general population (about 3 %) (Youssef et al. 2011).
Indeed, US guidelines recommend that children undergo-
ing evaluation for ADHD are assessed for sleep apnea
(Wolraich et al. 2011).
Surgical treatment of children with OSA via adenoton-
sillectomy in prospective, interventional studies has been
reported to be associated with improvements in neuropsy-
chological behavior (Beebe 2006), academic performance
(Gozal 1998) and ADHD-like symptoms (Soylu et al.
2013; Youssef et al. 2011). In children with diagnoses of
ADHD and OSA, two prospective studies have
Associations of sleep disturbance with ADHD 5
123
demonstrated significant improvements in ADHD symp-
toms, including hyperactivity, following adenotonsillec-
tomy (Chervin et al. 2006; Huang et al. 2007). There is also
some evidence that positive airway pressure ventilation in
patients with OSA may also be associated with improve-
ments in ADHD-like symptoms (Youssef et al. 2011).
Large-scale, randomized, controlled studies are warranted
to investigate further the effect of OSA treatment in
patients with ADHD (Youssef et al. 2011).
Restless legs syndrome and periodic limb movement
disorder
Restless legs syndrome (RLS) is a neurological disorder
characterized by an irresistible urge to move the legs to
relieve uncomfortable sensations at rest (Picchietti and
Picchietti 2010). Periodic limb movement disorder
(PLMD) is a clinical syndrome characterized by PLMS of a
specific nature and frequency determined by polysomnog-
raphy (Picchietti and Picchietti 2010). While 2 % of typi-
cally developing children and adolescents (aged
8–17 years) are reported to meet the diagnostic criteria for
RLS (Picchietti et al. 2007), up to 44 % of children with
ADHD have symptoms of RLS, and 26 % of children with
RLS have symptoms of ADHD (Cortese et al. 2005; Owens
2008). Accordingly, Cortese et al. have emphasized the
importance of identifying RLS during clinical evaluation of
children with ADHD symptoms (Cortese et al. 2006b). The
recently revised diagnostic criteria for RLS in children
introduced pediatric terms and prompts to allow the clini-
cian to recognize typical descriptions of RLS symptoms,
which must be in the child’s own words (Picchietti et al.
2013). As described previously, increased PLMS in
patients with ADHD compared with controls is a common
finding in polysomnographic studies. The impact of RLS or
PLMD on sleep could lead not only to the diurnal mani-
festation of ADHD-like symptoms but also to bedtime
resistance, which may be mistaken for opposition or defi-
ance, due to the unpleasant symptoms (Cortese et al.
2006b).
Circadian-rhythm sleep disorders
The major feature of circadian-rhythm sleep disorders is
the misalignment of sleep pattern timing with the terrestrial
cycle, leading to disrupted sleep and impaired functioning.
In delayed sleep-phase disorder, sleeping and waking occur
later than normal, and this may manifest as sleep onset
insomnia, evening diurnal preference and difficulty wak-
ing. Such sleep problems are common, especially during
adolescence: a meta-analysis of adolescent sleep studies
revealed a worldwide delayed sleep–wake behavior pattern
that was consistent with delayed sleep-phase disorder and
resulted in decreased total sleep time and daytime sleepi-
ness (Gradisar et al. 2011). There is evidence to suggest
that ADHD may be associated with disturbances of the
circadian rhythm. A delayed pattern of melatonin secretion
in children with ADHD compared with controls has been
described (Van der Heijden et al. 2005, 2007). Children
with ADHD have also been reported to exhibit stronger
circadian evening tendencies than controls, as assessed
using the child morning-evening preference scale. Scores
on this parent-rated instrument were correlated with both
parental and polysomnographic measures of sleep onset
latency (Gruber et al. 2012a). In adults with ADHD, dis-
turbances in diurnal rhythms of endocrine secretion,
CLOCK gene expression and physical activity have been
reported (Baird et al. 2012; Bijlenga et al. 2013). Fur-
thermore, delayed sleep timing in adults with ADHD and
comorbid insomnia compared with controls has been doc-
umented (Van Veen et al. 2010) and shown to correlate
with the severity of ADHD symptoms (Gamble et al.
2013).
Interaction of obesity with sleep disorders and ADHD
There is good evidence from cross-sectional studies for an
association of ADHD with obesity: The prevalence of
ADHD is higher than expected in people with obesity
sampled at obesity clinics, and the body mass index of
patients with ADHD is higher than average (Cortese et al.
2008a). Furthermore, in a 33-year longitudinal study,
41.4 % of adults who had combined-type ADHD as chil-
dren were obese, compared with 21.6 % of those without a
childhood diagnosis of ADHD (Cortese et al. 2013c).
Obesity is, in turn, correlated with sleep-disordered
breathing and other sleep disorders (Cortese et al. 2008b),
short sleep duration (Taheri et al. 2004) and short time in
bed (Hart et al. 2013). Abnormal eating behaviors associ-
ated with ADHD (e.g., impulsive eating) might contribute
to obesity (Cortese and Vincenzi 2012), and in adolescents
with obesity but without diagnosed ADHD, daytime
sleepiness has been reported to correlate with ADHD
symptom ratings (Cortese et al. 2007). Together, these data
suggest a complex interplay between ADHD, obesity and
sleep problems.
Effects of ADHD medications on sleep
ADHD medications are known to affect sleep in many
individuals, and guidelines recommend that sleep is care-
fully assessed before starting ADHD pharmacotherapy
(Graham et al. 2011; Wolraich et al. 2011). Sleep distur-
bances in patients with ADHD, including those associated
with ADHD medications, may be addressed via
6 A. Hvolby
123
pharmacological and behavioral interventions, with the
latter forming part of the recommended multimodal strat-
egy (Cortese et al. 2013a).
Pharmacotherapy with stimulants
The effects of stimulants on sleep in patients with ADHD
differ from patient to patient and reflect the underlying
complexity of the links between ADHD and sleep distur-
bance (Graham et al. 2011). The sympathomimetic action
of stimulants promotes wakefulness in most people,
underlying their use in the treatment of narcolepsy (Mor-
genthaler et al. 2007). While there is evidence that stimu-
lants are associated with disrupted or disturbed sleep in
patients with ADHD (Ironside et al. 2010; Nutt et al. 2007;
Spruyt and Gozal 2011; Stein 1999), clinical experience
also indicates that stimulants produce paradoxical effects
(Bradley 1937), whereby alleviation of symptoms can calm
patients and promote sleep (Jerome 2001; Kinsbourne
1973; Kooij et al. 2001; Kratochvil et al. 2005). Further-
more, because of the potential for symptom rebound as
blood drug concentrations wane (Carlson and Kelly 2003),
an additional dose of a short-acting stimulant, or the use of
a formulation with an increased duration of action, may
prevent sleep disturbances resulting from worsening of
hyperactivity or behavioral difficulties at bedtime (Cortese
et al. 2013a, b; Lecendreux et al. 2000).
In clinical trials using objective sleep measures, imme-
diate-release methylphenidate has been reported to increase
sleep onset latency and/or to decrease total sleep time in
patients with ADHD (Boonstra et al. 2007; Galland et al.
2010; Greenhill et al. 1983; Sangal et al. 2006), with sleep
quality either unaffected (Galland et al. 2010) or improved
(Boonstra et al. 2007; Sobanski et al. 2008). A recent meta-
analysis of six actigraphic studies in children with ADHD
reported statistically significant lower daytime activity,
longer sleep onset latency, lower total sleep time and lower
sleep efficiency with immediate-release methylphenidate
treatment than with placebo (De Crescenzo et al. 2014).
Both amfetamine and methylphenidate are associated with
treatment-emergent adverse events (TEAEs) of insomnia in
clinical studies (Efron et al. 1997; Stein et al. 2011).
Long-acting stimulants are available in many different
formulations (Hodgkins et al. 2012). This section focuses
on osmotic-release oral system methylphenidate (OROS-
MPH) and lisdexamfetamine dimesylate (LDX), both of
which are recently developed and widely used ADHD
medications with daily durations of efficacy of at least 12 h
post-dose (Coghill and Seth 2006; Lakhan and Kirchgess-
ner 2012; Setyawan et al. 2013a, b; Steer et al. 2012).
OROS-MPH combines an immediate-release bolus with
a two-stage extended-release technology to provide an
ascending profile of drug delivery similar to three daily
doses of immediate-release methylphenidate (Swanson
et al. 2003). In an open-label polysomnographic study in
children with ADHD, the only statistically significant
effects of OROS-MPH treatment were a decrease in the
number of night-time awakenings and an increase in the
percentage of stage 2 sleep, compared with pre-treatment
baseline (Kim et al. 2010). Based on parental sleep diaries,
both OROS-MPH and another extended-release methyl-
phenidate formulation led to statistically significant
reductions in total sleep time 1–4 weeks after initiation of
treatment in a randomized study in children with ADHD
(Lee et al. 2012). In a randomized, double-blind, placebo-
controlled study, the majority of children in all three
treatment groups (OROS-MPH, placebo or immediate-
release methylphenidate three times daily) continued to
have good or excellent sleep quality based on parent ratings
at 2 and 4 weeks after initiation of treatment (Wolraich
et al. 2001). Sleep quality was also rated as good or
excellent by parents after 1 and 12 months of open-label
OROS-MPH treatment in children with ADHD (Wilens
et al. 2003). Table 1 shows a summary of the proportions
of patients experiencing TEAEs of insomnia in random-
ized, double-blind, placebo-controlled, parallel-group
clinical studies of OROS-MPH.
LDX is the only stimulant prodrug. After oral admin-
istration, rate-limiting enzymatic hydrolysis of LDX in the
bloodstream releases the pharmacologically active d-am-
fetamine moiety from the lysine conjugate (Steer et al.
2012). LDX treatment was not associated with impairments
in sleep quality or quantity in clinical trials using objective
sleep measures in adults with ADHD (Adler et al. 2009a;
Surman and Roth 2011) and children with ADHD (Giblin
and Strobel 2011) (Fig. 2). Table 2 shows a summary of
the proportions of patients experiencing TEAEs of
insomnia in randomized, double-blind, placebo-controlled,
parallel-group clinical studies of LDX.
Pharmacotherapy with non-stimulants
In contrast to stimulants, somnolence is the most common
sleep-related adverse event associated with atomoxetine (a
noradrenaline reuptake inhibitor approved for treatment of
ADHD). In a 2009 systematic review, the frequency of
somnolence reported as a TEAE in placebo-controlled
clinical trials of atomoxetine was reported to range from 15
to 17 % (Garnock-Jones and Keating 2009). In a random-
ized, double-blind trial, atomoxetine was associated with a
smaller increase in sleep onset latency, a lower frequency
of insomnia, a higher frequency of somnolence and smaller
effects on subjective measures of sleep than methylpheni-
date taken three times daily (Sangal et al. 2006). Lower
frequencies of insomnia and higher frequencies of som-
nolence with atomoxetine than with long-acting stimulants
Associations of sleep disturbance with ADHD 7
123
have been reported as TEAEs in randomized, double-blind,
parallel-group efficacy studies (Dittmann et al. 2013;
Newcorn et al. 2008). Dosing in the evening rather than in
the morning has been found to reduce daytime somnolence
with atomoxetine (Block et al. 2009).
An extended-release formulation of guanfacine, a
selective a2-adrenoceptor agonist, is approved in North
America for the treatment of children and adolescents
with ADHD, both as a monotherapy and as an adjunct to
stimulant treatment. Somnolence is one of the most
commonly reported TEAEs in clinical trials of exten-
ded-release guanfacine (either alone or when co-
administered with a stimulant) (Faraone et al. 2013).
The effects of guanfacine on ADHD symptoms have
been suggested to be independent of its sedative prop-
erties (Kollins et al. 2011). Extended-release clonidine
(another selective a2-adrenoceptor agonist) is also
approved in North America with a similar indication
(Childress and Sallee 2012) and is associated with
somnolence (Cortese et al. 2013b).
Management of sleep problems in patients with ADHD
Both European and US guidelines recommend assessment
of sleep disturbance during evaluation of an individual for
suspected ADHD, and before initiation of pharmacother-
apy (Graham et al. 2011; Wolraich et al. 2011). This
approach enables any effects of the disorder on sleep to be
distinguished from those of medication (Cortese et al.
2013b). Clinicians have been advised to use sleep diaries
and questionnaires for routine screening and follow-up,
together with specific screening for RLS and polysom-
nography when a physical sleep disorder is suspected
(Cortese et al. 2013b). In developing a multimodal treat-
ment plan for patients with ADHD, consideration should be
given to interventions focused on improving sleep and
bedtime behavior (Lecendreux and Cortese 2007). Both
non-pharmacological and pharmacological interventions
are available for improving sleep in patients with ADHD,
and are applicable to sleep disturbance associated with
ADHD medication and with the disorder itself. Potential
Table 1 Frequency of TEAEs of insomnia (or similar) in randomized, double-blind, placebo-controlled, parallel-group clinical studies of
OROS-MPH in patients with ADHD
Study Age of population, years Duration, weeks Treatment (n) Proportion of patients
reporting a TEAE, %
Medori et al. (2008) 18–65 5 Placebo (96) 7.3
OROS-MPH (305) 13.4
Biederman et al. (2006) 19–60 6 Placebo (74) 5a
OROS-MPH (67) 18a
Biederman et al. (2010) 19–60 6b Placebo (109) 4c
OROS-MPH (114) 11c
Adler et al. (2009b) 18–65 7 Placebo (116) 5.2 (3.4)d
OROS-MPH (110) 9.1 (7.3)d
Newcorn et al. (2008) 6–16 6 Placebo (74) 1e
OROS-MPH (219) 13e
Atomoxetine (221) 7e
Findling et al. (2008) 6–12 7 Placebo (85) 4.7
OROS-MPH (91) 7.7
Transdermal methylphenidate (98) 13.3
Casas et al. (2013) 18–65 13 Placebo (97) 11.3 (2.1)d
OROS-MPH 54 mg (89) 14.6 (7.9)d
OROS-MPH 72 mg (92) 16.3 (9.8)d
Randomized-withdrawal studies are excluded
ADHD attention-deficit/hyperactivity disorder, OROS-MPH osmotic-release oral system methylphenidate, TEAE treatment-emergent adverse
eventa Frequency of ‘sleep problems’b Acute efficacy phasec TEAEs reported on two or more visitsd Frequency of initial insomniae Includes insomnia, initial insomnia, middle insomnia and late insomnia
8 A. Hvolby
123
strategies for managing sleep disturbances during treatment
with ADHD medications are summarized in Table 3.
Sleep hygiene
Healthy sleep practices include the following: a regular
sleep/wake schedule; adequate opportunity for sleep;
calming and structured bedtime routines; avoidance of
caffeine, large amounts of liquids, naps, exercise and
alerting activities (e.g., use of electronic devices) soon
before bedtime; sleeping only in bed and using the bed
only for sleeping; and attention to environmental factors
such as bedroom furniture, lighting and temperature
(Cortese et al. 2013a; Owens 2008; Yoon et al. 2012). In a
study of children with ADHD and initial insomnia
receiving stimulants, implementing sleep hygiene reduced
sleep onset delay to below 60 min in about 20 % of
patients, with an overall effect size of 0.67 (Weiss et al.
2006). Implementing healthy sleep practices is the rec-
ommended first-line option for addressing problems with
sleep in both medicated and un-medicated patients with
ADHD (Cortese et al. 2013b; Lecendreux and Cortese
2007).
Behavioral interventions
Established behavioral interventions for insomnia in typi-
cally developing children include parent education, grad-
uated extinction (ignoring disruptive behaviors for a
predetermined period) and bedtime fading, which involves
identifying a bedtime at which the child falls asleep within
about 15 min, and gradually setting bedtime earlier until
the desired bedtime is achieved, while keeping wake time
fixed and disallowing sleep at other times (Mindell et al.
2006; Vriend and Corkum 2011). Clinical studies of
behavioral interventions to improve sleep in children with
ADHD are limited and have not demonstrated any effect on
ADHD symptoms (Cortese et al. 2013a). A pilot study
indicated that a sleep program involving face-to-face and
telephone contact with a specialist pediatrician or child
psychiatrist improved children’s sleep, quality of life and
psychosocial functioning, based on parent reports after
5 months (Sciberras et al. 2011). This approach is under
evaluation in a larger randomized, controlled study (Scib-
erras et al. 2010). Case reports also indicate efficacy of
behavioral programs in reducing the severity of dyssomnia
in children with ADHD (Mindell et al. 2006).
Placebo
Late
ncy
to p
ersi
sten
t sle
ep (
min
utes
) Baseline Week 7 Change
0
2
4
6
8
10
Num
ber
of a
wak
enin
gs
0
20
40
60
80
100
Sle
ep e
ffici
ency
(%
)
–5
10
30
40
50
19.00
3.57
91.28
18.71
3.00
85.76
28.79
7.93
90.17
41.00
3.29*
93.27
–0.29
12.21
a
db
c
LDX
Placebo LDX Placebo LDX
Placebo LDX
Mea
n C
SH
Q s
core
20
15
35
45
25
5
0
–5
10
30
40
50
20
15
35
45
25
5
0
Baseline Week 7 Baseline Week 7
Baseline Week 7 Change
Fig. 2 a, b Polysomnographic,
c parent-rated subjective and
d actigraphic outcomes from a
double-blind, randomized,
parallel-group study of the
effects of LDX treatment on
sleep in 24 children with ADHD
(Giblin and Strobel 2011).
*p \ 0.0001 versus baseline.
ADHD attention-deficit/
hyperactivity disorder, CSHQ
Children’s Sleep Habits
Questionnaire, LDX
lisdexamfetamine
Associations of sleep disturbance with ADHD 9
123
The ball blanket
Ball blankets (Fig. 3) are filled with loose balls to stimulate
sensory receptors in the skin, muscles and joints, which
transmit inhibitory signals to the central nervous system
(Hvolby and Bilenberg 2011). In a study in children with
ADHD, the use of ball blankets was found to reduce sleep
onset latency, the number of awakenings and intra-indi-
vidual variability in sleep parameters (Hvolby and Bilen-
berg 2011).
Pharmacological strategies
In addition to adjusting dose, class, formulation or regimen
of ADHD medications, sleep problems in patients with
ADHD may be addressed via additional medications
(Table 3). In patients with psychiatric comorbidities, it
should be borne in mind that other medications (e.g.,
antidepressants) may also affect sleep. Implementation of
healthy sleep practices should precede pharmacological
interventions targeted at specific sleep disorders in patients
with ADHD (Cortese et al. 2013a).
Iron deficiency has been implicated in the etiology of
both RLS and ADHD, with potential links to alteration of
dopamine transporter expression and the synthesis and
catabolism of monoaminergic neurotransmitters (Allen and
Earley 2007; Cortese et al. 2005, 2012). A small, ran-
domized study of iron supplementation in children with
ADHD detected a statistically significant reduction of
ADHD symptoms (Konofal et al. 2008). Monitoring serum
ferritin levels has been proposed for children with sus-
pected RLS (Picchietti and Picchietti 2010), and there is
some evidence that iron supplementation may be effective
in relieving the symptoms of RLS in children (Cortese
et al. 2013a). The role of monoamine neurotransmission in
ADHD and RLS was investigated more directly in a dou-
ble-blind, placebo-controlled trial in 29 children with
ADHD or ADHD and RLS/PLMS. In this study, levodopa
treatment slightly improved PLMS and/or RLS symptoms,
but did not affect other sleep parameters, ADHD symptoms
Table 2 Frequency of TEAEs of insomnia (or similar) in randomized, double-blind, placebo-controlled, parallel-group clinical studies of LDX
in patients with ADHD
Study Age of population,
years
Duration,
weeks
Treatment
(n)
Proportion of patients
reporting a TEAE, %
Biederman et al. (2007) 6–12 4 Placebo (72) 2.8
LDX (218) 18.8
Adler et al. (2008) 18–55 4 Placebo (62) 5
LDX (358) 17–21a
Findling et al. (2011) 13–17 4 Placebo (77) 3.9
LDX (223) 11.2
Coghill et al. (2013) 6–17 7 Placebo (110) 0.0 (0.9)c
LDX (111) 14.4 (2.7)c
OROS-MPH (111)b 8.1 (6.3)c
Adler et al. (2013) 18–55d 10 Placebo (80) 3.8
LDX (79) 12.7
Randomized-withdrawal studies are excluded
ADHD attention-deficit/hyperactivity disorder, LDX lisdexamfetamine dimesylate, TEAE treatment-emergent adverse eventa Range across forced-dose groups (30, 50 or 70 mg/day)b Reference arm (active control)c Frequency of initial insomniad Patients with ADHD and executive function deficits
Table 3 Recommended strategies for managing sleep disturbances
during treatment with ADHD medications (Cortese et al. 2013b)
Monitoring: insomnia associated with stimulants may attenuate
after 1–2 months (Lecendreux and Cortese 2007)
Considering if it is possible to stop the medication
Implementing sleep hygiene/behavioral measures
Reviewing the possible causes of sleep problems
Treating RLS
Adding small, short-acting stimulant doses in the early evening
(if rebound effect occurs)
Reducing stimulant dose
Switching to an alternative class of stimulant
Switching to an alternative stimulant formulation
Considering use of a non-stimulant (e.g., atomoxetine)
Considering melatonin treatment
ADHD attention-deficit/hyperactivity disorder, RLS restless legs
syndrome
10 A. Hvolby
123
or performance in neuropsychometric tests (England et al.
2011). However, a subsequent subgroup analysis of this
study failed to confirm the effect of levodopa on PLMS
(Ferri et al. 2013). These results suggest that further work
is needed to unravel the relationship, if any, between
dopamine, ADHD and RLS/PLMS. No therapies have yet
received regulatory approval for treating RLS in children
(Cortese et al. 2013a).
Patients with ADHD and circadian-rhythm disorder are
reported to exhibit a delayed pattern of melatonin secre-
tion. Melatonin is classified as a dietary supplement in the
USA but is subject to drug regulation in Europe (Bendz and
Scates 2010). Two randomized, double-blind, placebo-
controlled trials (Van der Heijden et al. 2007; Weiss et al.
2006) and a preliminary open-label study (Tjon Pian Gi
et al. 2003) have indicated that melatonin treatment is
effective in reducing sleep onset delay in children with
ADHD (Cortese et al. 2013a).
Hypnotic agents, including zolpidem, mirtazapine,
trazodone and antihistamines, have been used off-label in
clinical practice to treat insomnia in children with ADHD
(Kratochvil et al. 2005) and some have been evaluated in
clinical trials (Cortese et al. 2013b), but their use does not
form part of current clinical guidelines. Clonidine has also
been suggested as a treatment option for stimulant-associ-
ated sleep onset delay in patients with ADHD (in an
immediate-release formulation rather than the extended-
release formulation used as an ADHD therapy) (Prince
et al. 1996; Wilens et al. 1994).
Real-world data on sleep medication use in patients with
ADHD is scarce. In observational study in a population of
children with ADHD, 63 % of whom had moderate or
severe sleep problems, 19 % took clonidine and 9 % took
melatonin during the 1-week reporting period (none took
antihistamines, benzodiazapenes or dopamine agonists)
(Efron et al. 2014).
A conceptual model of the interactions of ADHD
with sleep
Associations between ADHD and sleep disorders and
subjective or objective measures of sleep or sleep distur-
bance do not provide information on causation. As an
interpretative aid, this section presents a conceptual model
of the potential relationships between sleep problems and
ADHD or ADHD-like symptoms (Fig. 4). This theoretical
framework is made up of four hypothetical scenarios.
In one scenario, ADHD leads directly to problems with
sleep (Fig. 4, left-hand panel). This may be due to hyper-
activity, nocturnal motricity or behavior (e.g., bedtime
resistance). This scenario may be more pertinent to patients
with hyperactive symptoms than to those with predomi-
nantly inattentive ADHD. If sleep problems are a conse-
quence of ADHD symptoms, treatment with stimulants
may help a patient to sleep by reducing these symptoms.
Insufficient duration of efficacy may, however, lead to
symptom rebound at bedtime.
In a contrasting scenario, disturbed sleep is responsible
for daytime symptoms, behaviors and functional impair-
ments that are characteristic of ADHD (Fig. 4, right-hand
panel). The strongest evidence for a sleep disorder giving
rise to ADHD or ADHD-like symptoms is the amelioration
of such symptoms after surgical intervention to improve
nocturnal breathing. It has been recommended that primary
sleep disorders are excluded before diagnosing ADHD
(Cortese et al. 2006b, 2013a; Lecendreux and Cortese
2007). In this situation, psychostimulant medications might
be ineffective or could even exacerbate sleep problems. In
contrast, treating an underlying sleep disorder could result
in daytime improvements (O’Brien 2009). That successful
treatment of OSA, RLS and delayed sleep-phase disorder
can lead to improvements in ADHD symptoms is borne out
by case studies (Miano et al. 2013).
In another scenario, sleep disturbances and ADHD are
coincident, but may exacerbate each other in a feed-for-
ward loop (Fig. 4, upper-middle panel). Individuals with
ADHD could be both more vulnerable to the effects of
sleep disturbance and more prone to disturbed sleep than
typically developing children (Owens et al. 2013). The
Fig. 3 Ball blanket. a Plastic balls, diameter 49 mm and b cotton
blanket containing 7 kg of balls and measuring 140 9 200 cm
Associations of sleep disturbance with ADHD 11
123
choice of treatment in this situation is complex because
medications could have opposing or mixed effects on sleep.
Psychiatric comorbidities are common in children with
ADHD, and these may be associated with sleep problems.
Furthermore, daytime sleepiness has been reported to be
associated with worsened internalizing symptoms in chil-
dren with anxiety disorder, suggesting that poor sleep may
negatively affect emotional regulation as well as attentional
functioning (Hansen et al. 2013). The possible interplay
between sleep, ADHD and anxiety in children may be
related to the alterations observed in sleep-deprived indi-
viduals in overlapping brain mechanisms involved in
alertness and reward pathways (Gruber 2014). Sleep dis-
turbances in ADHD can, however, occur independently of
psychiatric comorbidities, as demonstrated in studies
employing psychiatric control groups (Hvolby et al. 2008).
Nevertheless, comorbid psychiatric disorders (both inter-
nalizing and externalizing) may further exacerbate both
sleep problems and ADHD symptoms in patients with
ADHD.
In a final scenario, common or overlapping neurobio-
logical disease mechanisms are hypothesized to give rise to
both ADHD and sleep disturbance (Fig. 4, lower-middle
panel). Circadian-rhythm disorders, sleep/wake disorders
and delayed sleep-phase disorder could share pathophysi-
ological mechanisms with ADHD. There may be a genet-
ically determined predisposition to sleep dysregulation in
at least a subset of individuals with ADHD (Owens et al.
2013). Intra-individual variability in neuropsychological
tasks, rather than a constant level of impairment, is char-
acteristic of ADHD (Spencer et al. 2009; Tamm et al.
2012), and a similar picture of volatility and unpredict-
ability is observed in sleep patterns in children with ADHD
(Gruber and Sadeh 2004; Gruber et al. 2000; Lecendreux
and Cortese 2007; Tsai and Huang 2010). Furthermore,
sleep duration decreases during development, and a more
rapid decrease compared with normative centiles at
3–5 years of age has been reported to be a significant
predictor of subsequent ADHD (Scott et al. 2013).
Conclusions
ADHD is commonly associated with specific sleep disor-
ders and objectively or subjectively assessed sleep distur-
bances. The relationship between ADHD and sleep
problems is complex and bidirectional, and is modulated by
interactions with ADHD medications and by psychiatric
comorbidities and associated medications. Understanding
these associations and relationships is important when
assessing and managing patients with ADHD. As recom-
mended in current guidelines, primary sleep disorders
(specifically SDB/OSA and PLMD/RLS) should be ruled
out before diagnosing or treating ADHD. Obesity and
Treating sleep disordermay alleviate ADHD
Integratedtreatmentapproach
Treating ADHD mayalleviate sleep problem
Sleep problem primarySleep disorders ordisturbances cause
or mimic ADHD
ADHD primaryADHD symptoms lead to
sleep disturbancesor disorders
Interaction and complexity
Reciprocal causation orcommon aetiology
Common underlyingpathophysiology
ADHD
Sleep problem
ADHD
Sleep problem
Comorbidity(depression,
anxiety)
Neuro-behavioural
morbidityADHD
Sleep problem
ADHDor ADHD-like symptoms
Sleep problem
Fig. 4 Conceptual model of the
modes of interaction between
ADHD and sleep. ADHD
attention-deficit/hyperactivity
disorder
12 A. Hvolby
123
psychiatric comorbidities (e.g., anxiety and depression) can
also lead to sleep problems, and need to be identified and
treated appropriately. The multifaceted effects of stimulant
pharmacotherapy on sleep in patients with ADHD are
particularly important for clinicians to understand when
evaluating treatment options for patients. Stimulant medi-
cations may disrupt or improve sleep in different patients,
depending not only on the nature of the patient’s illness,
but also on the drug dose, class, formulation and duration
of efficacy. Effective management of sleep problems
associated with ADHD and its treatment may not only
alleviate sleep-related symptoms, but also improve quality
of life in parents or carers of children with disruptive
bedtime behavior or insomnia.
In the near term, new understanding of how sleep
interacts with ADHD and how this affects treatment
choices is likely to come from clinical studies. Polysom-
nographic studies need to be larger and better controlled
than previous studies, and should not overlook subtle
polysomnographic signals such as microarousals and the
time structure of PLMS. There is also a need to follow up
the recent data indicating a link between ADHD, obesity,
daytime sleepiness and circadian-rhythm alterations. Con-
spicuously absent from the current literature is any con-
vincing demonstration that pharmacological or non-
pharmacological intervention to improve sleep actually
leads to improved ADHD symptoms or reduced functional
impairment associated with the disorder. Similarly, as
children become adolescents, they may experience sleep
loss, but do any adolescents benefit from more or better
sleep in terms of preventing worsening of ADHD? Crucial
to both these questions is the possibility that specific
ADHD phenotypes are associated with, or characterized
by, particular types of sleep-related problems. In addition
to helping clinicians make treatment decisions, the ability
to subcategorize patients with ADHD based on their sleep
phenotype may help shed light on areas where current data
are conflicting. Furthermore, such phenotypic classification
is probably essential for increased sensitivity in genomic
screens for ADHD-associated polymorphisms. The over-
lapping neurochemical and neuroanatomical systems
involved in regulating sleep, attention, arousal and circa-
dian rhythms are the subjects of current basic research
(Owens et al. 2013). Whether enhanced understanding of
these mechanisms in health and disease or the use of state-
of-the-art genetic and neuroimaging tools will lead to the
development of new therapies or preventative strategies for
ADHD are questions for the future.
Acknowledgments Shire provided funding to Oxford PharmaGen-
esisTM Ltd for writing and editorial support for this publication. Dr.
M. Cottingham and Dr. E. Southam of Oxford PharmaGenesisTM Ltd
provided writing assistance under the direction of the author. Editorial
assistance in editing, fact checking, formatting, proofreading and
submission was also provided by Oxford PharmaGenesisTM Ltd. Shire
develops and markets drugs to treat psychiatric disorders, including
ADHD.
Conflict of interest The author declares he has no conflict of
interest.
Open Access This article is distributed under the terms of the
Creative Commons Attribution License which permits any use, dis-
tribution, and reproduction in any medium, provided the original
author(s) and the source are credited.
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